Tackling Ischemic Reperfusion Injury With the Aid of Stem Cells and Tissue Engineering

Mauricio Zamorano, Rodrigo L. Castillo, Jorge F. Beltran, Lisandra Herrera, Joaquín A. Farias, Christian Antileo, Cristobal Aguilar-Gallardo, Adalberto Pessoa, Yolanda Calle, Jorge G. Farias

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Ischemia is a severe condition in which blood supply, including oxygen (O), to organs and tissues is interrupted and reduced. This is usually due to a clog or blockage in the arteries that feed the affected organ. Reinstatement of blood flow is essential to salvage ischemic tissues, restoring O, and nutrient supply. However, reperfusion itself may lead to major adverse consequences. Ischemia-reperfusion injury is often prompted by the local and systemic inflammatory reaction, as well as oxidative stress, and contributes to organ and tissue damage. In addition, the duration and consecutive ischemia-reperfusion cycles are related to the severity of the damage and could lead to chronic wounds. Clinical pathophysiological conditions associated with reperfusion events, including stroke, myocardial infarction, wounds, lung, renal, liver, and intestinal damage or failure, are concomitant in due process with a disability, morbidity, and mortality. Consequently, preventive or palliative therapies for this injury are in demand. Tissue engineering offers a promising toolset to tackle ischemia-reperfusion injuries. It devises tissue-mimetics by using the following: (1) the unique therapeutic features of stem cells, i.e., self-renewal, differentiability, anti-inflammatory, and immunosuppressants effects; (2) growth factors to drive cell growth, and development; (3) functional biomaterials, to provide defined microarchitecture for cell-cell interactions; (4) bioprocess design tools to emulate the macroscopic environment that interacts with tissues. This strategy allows the production of cell therapeutics capable of addressing ischemia-reperfusion injury (IRI). In addition, it allows the development of physiological-tissue-mimetics to study this condition or to assess the effect of drugs. Thus, it provides a sound platform for a better understanding of the reperfusion condition. This review article presents a synopsis and discusses tissue engineering applications available to treat various types of ischemia-reperfusions, ultimately aiming to highlight possible therapies and to bring closer the gap between preclinical and clinical settings.

© 2021, The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0/
Original languageEnglish
Pages (from-to)705256
JournalFrontiers in physiology
Early online date17 Sept 2021
Publication statusPublished - 2021


  • Physiology
  • ischemia reperfusion injury
  • stem cells
  • tissue engineering
  • 3D culture
  • IRI mechanism

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